WO2023275740A1 - Compositions destinées au traitement de l'hypopigmentation - Google Patents

Compositions destinées au traitement de l'hypopigmentation Download PDF

Info

Publication number
WO2023275740A1
WO2023275740A1 PCT/IB2022/055989 IB2022055989W WO2023275740A1 WO 2023275740 A1 WO2023275740 A1 WO 2023275740A1 IB 2022055989 W IB2022055989 W IB 2022055989W WO 2023275740 A1 WO2023275740 A1 WO 2023275740A1
Authority
WO
WIPO (PCT)
Prior art keywords
topical composition
extract
linearis
ethanolic extract
skin
Prior art date
Application number
PCT/IB2022/055989
Other languages
English (en)
Inventor
Analike Blom VAN STADEN
Namrita Lall
Original Assignee
University Of Pretoria
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by University Of Pretoria filed Critical University Of Pretoria
Priority to US18/574,200 priority Critical patent/US20240285710A1/en
Publication of WO2023275740A1 publication Critical patent/WO2023275740A1/fr

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/96—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution
    • A61K8/97—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution from algae, fungi, lichens or plants; from derivatives thereof
    • A61K8/9783—Angiosperms [Magnoliophyta]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/48—Fabaceae or Leguminosae (Pea or Legume family); Caesalpiniaceae; Mimosaceae; Papilionaceae
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/14—Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/32—Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers, poly(meth)acrylates, or polyvinyl pyrrolidone
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
    • A61K8/37—Esters of carboxylic acids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/72—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds
    • A61K8/81—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds obtained by reactions involving only carbon-to-carbon unsaturated bonds
    • A61K8/8141—Compositions of homopolymers or copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and at least one being terminated by only one carboxyl radical, or of salts, anhydrides, esters, amides, imides or nitriles thereof; Compositions of derivatives of such polymers
    • A61K8/8152—Homopolymers or copolymers of esters, e.g. (meth)acrylic acid esters; Compositions of derivatives of such polymers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/72—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds
    • A61K8/81—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds obtained by reactions involving only carbon-to-carbon unsaturated bonds
    • A61K8/8141—Compositions of homopolymers or copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and at least one being terminated by only one carboxyl radical, or of salts, anhydrides, esters, amides, imides or nitriles thereof; Compositions of derivatives of such polymers
    • A61K8/8158—Homopolymers or copolymers of amides or imides, e.g. (meth) acrylamide; Compositions of derivatives of such polymers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/92—Oils, fats or waxes; Derivatives thereof, e.g. hydrogenation products thereof
    • A61K8/922—Oils, fats or waxes; Derivatives thereof, e.g. hydrogenation products thereof of vegetable origin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/96—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution
    • A61K8/97—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution from algae, fungi, lichens or plants; from derivatives thereof
    • A61K8/9783—Angiosperms [Magnoliophyta]
    • A61K8/9789—Magnoliopsida [dicotyledons]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0014—Skin, i.e. galenical aspects of topical compositions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/06—Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/10—Dispersions; Emulsions
    • A61K9/107—Emulsions ; Emulsion preconcentrates; Micelles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
    • A61K2236/30—Extraction of the material
    • A61K2236/33—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones

Definitions

  • the present invention relates to the use of a composition comprising an extract from the plant Aspalathus linearis in preventing or treating hypo-pigmented disorders of the skin.
  • the invention also relates to methods of preventing or treating hypo-pigmented disorders of the skin using compositions comprising an extract from the plant Aspalathus linearis.
  • hypopigmentation disorders a problem faced worldwide, are due to reduced melanin production in the melanocytes and often due to the obstruction of melanosome transfer.
  • a reduction in melanogenesis is generally due to decreased tyrosinase activity, lack of melanin precursors and reduced expression of the genes regulating melanogenesis.
  • Microfibrils and particular receptors within melanocyte dendrites are required for the transfer of melanosomes from melanocytes to keratinocytes. Hypopigmentation, therefore, occurs concurrently with a decrease in the rate of melanosome transfer.
  • Hypopigmentary disorders can either be genetic, as is the case with albanism, or acquired.
  • acquired hypopigmentated disorders are idiopathic guttate hypomelanosis, pityriasis alba, progressive macular hypomelanosis, post- inflammatory hypopigmentation, leukoderma and vitiligo.
  • pigmentation disorders remain challenging to treat.
  • the prevalence of hypopigmentation ranges from 0.06 to 2.28%, with an average of 1% worldwide, this accounts for 76 000 000 people.
  • the hypopigmented lesions in pityriasis alba patients have been shown to develop due to reduced melanin transfer from the melanocytes to the keratinocytes and an increase in damaged melanocytes.
  • hypopigmentation diseases include surgical based therapies, phototherapy and steroidal therapies; however, each treatment is associated with side effects.
  • short-term use of corticosteroids has resulted in headaches, electrolyte abnormalities, viral infection, pancreatitis, hypertension, skin atrophy, perioral dermatitis, rosacea, purpura, acne, delayed wound healing, hypertrichosis, pigmentation alterations and exacerbation of skin infections, and hematologic and neuropsychologic effects.
  • UV radiation is not harmful, overexposure to UV may lead to increased skin aging, and the development of melanomas and squamous cell cancers.
  • many of the current treatments for hypopigmentary disorders primarily focus on the reduction of melanin production, but few studies are aimed at stimulating melanin production in areas where there is a lack of pigment.
  • the present invention is aimed at determining how Aspalathus linearis (Burm.f.) R. Dahlgren (Fabaceae) could aid in the regulation of melanin production and melanin transfer for hypopigmentary disorders.
  • A. linearis is a woody shrub that belongs to the Fabaceae family.
  • A. linearis commonly known as Rooibos, is endemic to the Western Cape in South Africa. Rooibos tea has been traditionally used for medicinal purposes for numerous years.
  • the popularity and utilisation of A. linearis has since progressed from being limited to a herbal tea to the use in cosmeceutical products, nutraceuticals and as extracts used in beverages and food. More than 80% of A. linearis produced is exported and is currently sold in more than 37 countries in the world.
  • the present invention relates to topical compositions comprising of or consisting of a 100 pg/rnL ethanolic extract from the plant Aspalathus linearis together with a dermatologically acceptable carrier for use in a method of preventing or treating a hypopigmentary disorder of skin in a subject comprising applying the topical composition to the skin of the subject.
  • the invention also relates to methods of preventing or treating a hypopigmentary disorder of skin in a subject comprising applying the topical composition to the skin of the subject.
  • a topical composition comprising of or consisting of a 100 pg/rnL ethanolic extract from the plant Aspalathus linearis and dermatologically acceptable carrier for use in a method of preventing or treating a hypopigmentary disorder of skin in a subject, the method comprising applying the topical composition to the skin of the subject.
  • the topical composition comprises a 100 pg/mL ethanolic extract from the plant Aspalathus linearis, acrylates/Cio-30 alkyl acrylate crosspolymer, glycerin, caprylic/capric triglyceride, isopropyl myristate, dicaprylyl carbonate, acrylate/acrylamide copolymer dispersed in oil and polysorbate-85, a phenoxyethanol and ethylhexylglycerin preservative blend, water, and a dermatologically acceptable carrier.
  • the ethanolic extract from the plant Aspalathus linearis is a crude extract.
  • the topical composition is a lotion, cream, gel, serum, or emulsion.
  • the topical composition may comprise or consist of one or more additive selected from the group comprising of or consisting of a rheology modifier, a suspending agent, a thickener, a denaturant, a humectant, a solvent, an emollient, an emulsifier and/or a preservative.
  • the topical composition comprises or consists of the following: a) 100 pg/rnL crude ethanolic extract from the plant Aspalathus linearis ⁇ , b) acrylates/Cio-3o alkyl acrylate crosspolymer, preferably 1 to 10 mg/ml_ acrylates/Cio-3o alkyl acrylate crosspolymer; c) glycerin, preferably 10 to 50 mg/ml_ glycerin; d) caprylic/capric triglyceride, preferably 25 to 100 mg/ml_ caprylic/capric triglyceride; e) isopropyl myristate, preferably 5 to 50 mg/ml_ isopropyl myristate; f) dicaprylyl carbonate, preferably 5 to 50 mg/ml_ dicaprylyl carbonate; g) acrylate/acrylamide copolymer dispersed in oil and polysorbate-85, preferably 5 to
  • hypopigmentary disorder is selected from the group consisting of or comprising of idiopathic guttate hypomelanosis, pityriasis alba, progressive macular hypomelanosis, post- inflammatory hypopigmentation, leukoderma, vitiligo and hypopigmented scarring.
  • the topical composition stimulates melanin production and/or melanin transfer.
  • a method of preventing or treating a hypopigmentary disorder of skin in a subject comprising applying a topical composition to the skin of the subject, wherein the topical composition comprises a 100 pg/rnL ethanolic extract from the plant Aspalathus linearis, and a dermatologically acceptable carrier.
  • the topical composition comprises a 100 pg/rnL ethanolic extract from the plant Aspalathus linearis, acrylates/Cio-30 alkyl acrylate crosspolymer, glycerin, caprylic/capric triglyceride, isopropyl myristate, dicaprylyl carbonate, acrylate/acrylamide copolymer dispersed in oil and polysorbate-85, a phenoxyethanol and ethylhexylglycerin preservative blend, water, and a dermatologically acceptable carrier.
  • the ethanolic extract from the plant Aspalathus linearis is a crude extract.
  • the topical composition is a lotion, cream, gel, serum, or emulsion.
  • the topical composition may comprise or consist of one or more additive selected from the group comprising of or consisting of a rheology modifier, a suspending agent, a thickener, a denaturant, a humectant, a solvent, an emollient, an emulsifier and/or a preservative.
  • the topical composition comprises or consists of the following: a) 100 pg/mL crude ethanolic extract from the plant Aspalathus linearis ⁇ , b) acrylates/Cio-3o alkyl acrylate crosspolymer, preferably 1 to 10 mg/ml_ acrylates/Cio-3o alkyl acrylate crosspolymer; c) glycerin, preferably 10 to 50 mg/ml_ glycerin; d) caprylic/capric triglyceride, preferably 25 to 100 mg/ml_ caprylic/capric triglyceride; e) isopropyl myristate, preferably 5 to 50 mg/ml_ isopropyl myristate; f) dicaprylyl carbonate, preferably 5 to 50 mg/ml_ dicaprylyl carbonate; g) acrylate/acrylamide copolymer dispersed in oil and polysorbate-85,
  • hypopigmentary disorder is selected from the group consisting of or comprising of idiopathic guttate hypomelanosis, pityriasis alba, progressive macular hypomelanosis, post- inflammatory hypopigmentation, leukoderma, vitiligo and hypopigmented scarring.
  • the topical composition stimulates melanin production and/or melanin transfer.
  • a topical composition comprising of or consisting of a 100 pg/mL ethanolic extract from the plant Aspalathus linearis, acrylates/Cio-30 alkyl acrylate crosspolymer, glycerin, caprylic/capric triglyceride, isopropyl myristate, dicaprylyl carbonate, acrylate/acrylamide copolymer dispersed in oil and polysorbate-85, a phenoxyethanol and ethylhexylglycerin preservative blend, water, and a dermatologically acceptable carrier.
  • the ethanolic extract from the plant Aspalathus linearis is a crude extract.
  • the topical composition is a lotion, cream, gel, serum, or emulsion.
  • the topical composition may comprise or consist of one or more additive selected from the group comprising of or consisting of a rheology modifier, a suspending agent, a thickener, a denaturant, a humectant, a solvent, an emollient, an emulsifier and/or a preservative.
  • the topical composition comprises or consists of the following: a) 100 pg/mL crude ethanolic extract from the plant Aspalathus linearis ⁇ , b) acrylates/Cio- 30 alkyl acrylate crosspolymer, preferably 1 to 10 mg/ml_ acrylates/Cio- 30 alkyl acrylate crosspolymer; c) glycerin, preferably 10 to 50 mg/ml_ glycerin; d) caprylic/capric triglyceride, preferably 25 to 100 mg/ml_ caprylic/capric triglyceride; e) isopropyl myristate, preferably 5 to 50 mg/ml_ isopropyl myristate; f) dicaprylyl carbonate, preferably 5 to 50 mg/ml_ dicaprylyl carbonate; g) acrylate/acrylamide copolymer dispersed in oil and polysorbate-85,
  • Figure 2 Melanin transfer between the melanocytes or dendritic cells and keratinocytes (grey cells) in untreated cells. The nuclei of both types of cells were indicated by the round bodies present in the cells. Keratinocytes positive for melanin transfer have bright white dots (melanosomes) around their nuclei. The scale bar represents 10 pm.
  • Figure 3 Melanin transfer between the melanocytes - dendritic cells - and keratinocytes (grey cells) in cells treated with a-MSH.
  • the nuclei of both type of cells were indicated by the round bodies present in the cells.
  • Keratinocytes positive for melanin transfer have bright white dots (melanosomes) around their nuclei.
  • the brighter white dendrite tips indicate a higher concentration of melanosomes present.
  • the scale bar represents 10 pm.
  • Figure 4 Melanin transfer between the melanocytes - dendritic cells - and keratinocytes (grey cells) in cells treated with A. linearis. The nuclei of both type of cells were indicated by the round bodies present in the cells. Keratinocytes positive for melanin transfer have bright white dots (melanosomes) around their nuclei. The brighter white dendrite tips indicate a higher concentration of melanosomes present. The scale bar represents 10 pm.
  • Figure 5 Effect of Aspalathus linearis (AL) and a-MSH (positive control) on the amount of positive keratinocytes (melanosomes present around the nucleus of the keratinocytes) indicating melanin transferred compared to the untreated cells.
  • AL Aspalathus linearis
  • a-MSH positive control
  • R.Dahlgren determined over 12 weeks in glass jars. The amber brown liquid darkened at week 1 when stored at 40 °C and 50 °C.
  • the invention in its broadest form relates to a composition
  • a composition comprising an extracts derived from A. linearis.
  • the composition displays activity for the stimulation of melanin production and/or melanin transfer.
  • the composition is useful for preventing or treating a hypopigmentary disorder of the skin in a subject.
  • Melanogenesis is the synthesis of melanin, in the form of pigment granules called melanosomes, and occurs in the melanocytes. Melanin transfer occurs as soon as the melanin produced in the melanocytes has reached maturity and moved to the tip of the dendrites. Melanin transfer occurs naturally within the cell as was noticeable in the untreated cells, but could be influenced (induced or inhibited) by other treatments with compounds and plant extracts.
  • the Applicant has found that extracts of A. linearis stimulate melanin production.
  • the melanin production stimulated by the composition comprising an extract of A. linearis according to the present invention may be due to the presence of aspalathin (a phytoestrogen similar to glycyrrhizin), quercetin - which plays a key role in modulation of melanogenesis - and cytokinins (plant hormones), which increase the levels of tyrosinase.
  • aspalathin a phytoestrogen similar to glycyrrhizin
  • quercetin - which plays a key role in modulation of melanogenesis -
  • cytokinins plant hormones
  • compositions comprising an extract of A. linearis may provide an alternative treatment for hypopigmentation disorders, especially in cases of reduced pigmentation in particular those that are due to a reduction in melanin production or a hindrance in melanin transfer.
  • a plant-based composition with low cytotoxicity, provides a safer alternative to current treatments.
  • the extract of A. linearis exhibits a negligible effect on cellular proliferation of human melanoma cells (UCT-Mel1) with 50 % cell viability concentrations higher than 200 pg/mL, indicating low to no toxicity.
  • the ethanolic extract of A. linearis has further been shown not to be mutagenic.
  • the ethanolic extract of A. linearis was identified as a non-irritant.
  • Compositions of the present invention comprising the ethanolic extract of A. linearis have been shown to be stable at all storage conditions.
  • compositions of the present invention comprising the ethanolic extract of A. linearis at a concentration of 100 pg/mL in finished formulation resulted in significant repigmentation of 21% in the non-pigmented zones compared to the pigmented zones, which was observed in 88% of the volunteers in a clinical study.
  • composition of the invention may be in the form of a pharmaceutical or cosmeceutical composition.
  • the composition may be administered to a subject prior to a symptomatic state associated with hypopigmentary disorders, or after a symptomatic onset of hypopigmentary disorders in the subject.
  • the solvent may be an organic solvent.
  • Organic solvents typically used in the preparation of plant extracts include ethanol, methanol, butanol dichloromethane, chloroform, acetone and/or mixtures thereof.
  • the organic solvent is ethanol.
  • the term “crude extract” refers to a concentrated preparation of a plant extract obtained by removing secondary metabolites from the crude plant material with the aid of a suitable solvent. This may be done, for example, by submerging the crude plant material in the suitable solvent, removing the solvent and consequently evaporating all or nearly all of the solvent.
  • the term “purified extract” refers to an extract obtained by separating the constituent parts of the crude extract from each other. By way of a non-limiting example, the constituent parts of the crude extract may be separated from one another by separating the polar constituents from the non-poiar constituents. In so doing the active polar and/or non polar constituents may thus be concentrated.
  • composition of the present invention is a composition suitable for topical use on a subject.
  • the subject may include a living animal, preferably a mammal and most preferably a human.
  • the composition may include a dermatologically acceptable vehicle, carrier and/or diluent.
  • the pharmaceutical composition of the invention containing the extract may be in a form suitable for topical use. Suitable forms of the pharmaceutical composition include, for example, gels, lotions, creams, essences, toners, emulsions, soaps, shampoos, rinses, cleansers, solutions, ointments, jellies or suspensions.
  • the composition may be a topical composition in the form of a lotion, cream, gel, serum, or emulsion
  • suitable forms of the pharmaceutical composition may be combined with “pharmaceutically acceptable carriers” and other elements known in the art to produce creams, gels and lotions for use for general skin care.
  • the pharmaceutical composition may further be combined with other ingredients which promote absorption by the skin.
  • the extract may be formulated as a pharmaceutical composition by methods known to those skilled in the art.
  • Pharmaceutically acceptable ingredients may be used.
  • pharmaceutically acceptable refers to properties and/or substances which are acceptable for administration to a subject from a pharmacological or toxicological point of view. Further “pharmaceutically acceptable” refers to factors such as formulation, stability, patient acceptance and bioavailability which will be known to a manufacturing pharmaceutical chemist from a physical/chemical point of view.
  • compositions of the invention may further include additives which enhance the properties of the composition.
  • additives include, but are not limited to rheology modifiers, suspending agents, thickeners, denaturants, humectants, solvents, emollients, emulsifiers and preservatives.
  • compositions containing the extract entails administration of an effective amount of the pharmaceutical composition containing the extract to a subject in order to prevent or treat a condition.
  • effective amount in the context of preventing or treating a condition refers to the administration of an amount of the active plant extract to an individual in need of treatment, either a single dose or several doses of the pharmaceutical composition containing the extract.
  • the effective amount is a concentration in the range of about 100 pg/mL to about 300 pg/mL of the crude extract in the composition, such as about 100 pg/mL, about 150 pg/mL, about 200 pg/mL, about 250 pg/mL, or about 300 pg/mL of extract in the composition.
  • the effective amount of the crude extract in the composition is about 100 pg/mL.
  • suitable dosages of the extract and/or pharmaceutical composition containing the extract Although some indications have been given as to suitable dosages of the extract and/or pharmaceutical composition containing the extract, the exact dosage and frequency of administration of the effective amount will be dependent on several factors. These factors include the individual components used, the formulation of the pharmaceutical composition containing the extract, the condition being treated, the severity of the condition, the age, weight, health and general physical condition of the subject being treated, and other medication that the subject may be taking, and other factors as are known to those skilled in the art.
  • Dried plant material of A. linearis was obtained from Rooibos Ltd. (GPS coordinates: S 32° 11.131' EO 18° 53.291') in Clanwilliam.
  • a herbarium voucher specimen (PRU: 122176) was deposited at the H.G.W.J. Schweickerdt Herbarium, University of Pretoria, South Africa.
  • the coarsely ground (0.4 mm) plant material (13.85 kg) was extracted with 34 L of EtOH.
  • the ethanolic extract of A. linearis (ALEtOH) was filtered with a Buchner funnel (Whatman No. 3 filter paper), concentrated using a rotary evaporator at 40 °C and freeze-dried to a fine powder. The percentage yield of the freeze-dried extract was 9.03 % of the dried plant material.
  • Cells (2 x 10 4 cells/well in 1.9 ml of MEM) were inoculated into 24-well plates using a pipette (FALCON 353046, Becton Dickinson Labware, NJ, U.S.A.), and incubated for 24 hours at 37°C in the CO2 incubator.
  • the amount of melanin produced in the B16-F10 mouse melanocytes was determined spectrophotometrically.
  • the cells treated with unfermented A. linearis exhibited a significant increase in the concentration of melanin present extracellularly, with no significant increase of melanin present intracellularly.
  • DMEM Dulbecco's Modified Eagle's Medium
  • the 24-hour co-cultured cells were washed with PBS and fixed with MeOH (added at a temperature of -20°C) and incubated for 4 minutes at -20°C.
  • the fixed cells were washed with PBS to remove all the MeOH and incubated for 1 hour at room temperature with goat serum (0.5% in PBS) to remove effects of background noise.
  • the coverslips were removed from the goat serum and placed on filter paper.
  • Primary antibody staining consisted of anti-melanoma associated antigen (NKI/betab) at a ratio of 1 :100 in PBS and anti-wide spectrum cytokeratin antibody at a ratio of 1 :200 in PBS. Thirty microliters of primary antibody was added to each coverslip and incubated at room temperature for 1 hour.
  • the coverslips were washed with PBS to remove any unbound antibodies. Thirty microliters of secondary antibodies, (Alexa 488 and Alexa 555) at a ratio of 1 :500 in PBS, was added to the coverslips and incubated at room temperature for 1 hour and kept out of direct light. The coverslips were washed with PBS to remove any unbound antibodies and 300 to 500 mI of DAPI (4',6-diamidino-2-phenylindole) was added to stain the nuclei. The coverslips were incubated at room temperature for 5 min and washed with PBS. The washed coverslips were transferred to microscope slides containing mounting media and stored covered at 4°C, until analysed using the fluorescent microscope.
  • DAPI 4,6-diamidino-2-phenylindole
  • Table 1 Statistical significance between the results obtained for melanin transfer after 24 hours of treatment.
  • a significant difference between the untreated cells and the treated cells was obtained when analysed with the One way ANOVA test, with a P-value smaller than 0.001 (probability of approximately 1 in 1 x 10 6 of obtaining the observed differences between the means by coincidence).
  • the difference between the mean values of a-MSH and A. linearis were insignificant as the P-values were larger than 0.05, however, the concentration of a-MSH was much higher than the concentrations analysed for A. linearis.
  • the difference between the mean values of A. linearis (60 mV/GhI) and A. linearis (80 pg/ml) were insignificant as the P-values were larger than 0.05, therefore, both concentrations had similar effects on melanin transfer.
  • the antiproliferative activity of an ethanolic extract of Aspalathus linearis was determined on human melanoma cells (UCT-Mel1). The cells were maintained in Dulbecco's Modified Eagle's Medium (DMEM), supplemented with 10% fetal bovine serum (FBS) and 1 % antibiotics (Penicillin-Streptomycin). Cells were seeded in 96-well plates (100 000 cells/mL) and incubated overnight at 37 °C in 5% C02 to allow for attachment.
  • DMEM Dulbecco's Modified Eagle's Medium
  • FBS fetal bovine serum
  • antibiotics Penicillin-Streptomycin
  • the cells were treated with varying concentrations of the samples (1.56 to 200 pg/mL) and the positive control (actinomycin D, 0.0039 to 0.5 pg/mL) for 72 hours at 37 °C in 5% C02.
  • An untreated cell control and solvent control (DMSO 0.5%) were included in the experiment.
  • 20 pL Presto blue reagent was added to all the wells, and the plates were further incubated for an additional 3 hours.
  • the cell viability was determined by measuring the fluorescence at an excitation of 560 nm and emission of 590 nm using a Perkin Elmer VICTOR Nivo microplate reader. The concentration where 50 % of the cell viability was inhibited was calculated by normalising the data to the untreated cell control.
  • the extract of A. linearis exhibited negligible effect on cellular proliferation with 50 % cell viability concentrations higher than 200 pg/mL, indicating low to no toxicity.
  • the mutagenicity of an ethanolic extract of A. linearis was determined with Ames test using the S. typhimurium strain TA100.
  • the tester strain (TA-100) used in this study was selected based on its accuracy in detecting various known mutagens and is one of the recommended strains by the pharmaceutical industry (Purves et al., 1995). Briefly, the bacteria were cultured in Oxoid Nutrient broth at 37 °C for 16 hours on a rotative shaker. This overnight culture (100 pi) was mixed with 2 mL of top agar (containing histidine-biotin), 100 pi test solution and 500 pi phosphate buffer. The mixture was poured onto the minimal agar plate and incubated for 37 °C for 48 hours.
  • the plates did not have any visible differences, indicating a lack of toxicity towards the bacterial cells.
  • the number of spontaneous revertants observed for the negative and solvent control, and the ethanolic extract of A. linearis was in all cases within normal limits (Mortelmans and Zeiger, 2000), indicating that the ethanolic extract of A. linearis is not mutagenic (Table 2).
  • the similarity of the tested sample to the negative control indicated that the ethanolic extract of A. linearis was not toxic toward the bacteria at the concentration tested. This is in accordance with previous reports that both the fermented and unfermented aqueous extracts of A.
  • Table 2 The number of revertants (his- to his+) per plate for the bacterium Salmonella typhimurium determined using Ames test treated with the ethanolic extract of Aspalathus linearis (Burm.f.) R.Dahlgren and tested in triplicate. a Positive control; b untreated control; c Solvent control; d T-test was conducted between the samples and the negative control
  • the ethanolic extract of A. linearis was submitted for patch testing.
  • the sample was prepared to a concentration of 300 pg/mL (final concentration of the sample in formulation) in 60% EtOH and distilled water.
  • the concentration of the extract was below the concentration (345.5 ⁇ 2.47 pg/mL) resulting in 50% cell viability determined in human melanocytes.
  • the sample was transferred to 8mm Finn Chambers on micropore tape, together with the positive control (a known irritant) and negative control (demineralised water), which were used in an occlusive patch testing. Visual assessments and colour photographs of the test sub-sites were made at 24, 48 and 72 hours.
  • the different ratings provided a mean score for the samples. If the mean score (average plus standard deviation) of the samples has a similar score or falls below that of the negative control, the samples were considered a non-irritant. If the mean score of the samples falls above that of negative control but was lower than that of positive control, the sample is regarded as a mild irritant. If the mean score of the samples falls above that of the positive control the sample is considered an irritant.
  • the stability of the extract was determined to establish its shelf life, which included the expiration date for the utilisation of the product after opening.
  • the stability data provides the correct storing data for the clinical trials and indicates whether the product will remain stable throughout the trial period.
  • the ethanolic extract was re-dissolved in 60% EtOH and distilled water to a concentration of 6000 pg/mL, of which 5% was added to the finished formulation.
  • the final concentration in formulation was similar to the bioactive concentration in vitro.
  • the stability of the ethanolic extract of A. linearis alone (6000 pg/mL) and in a formulation (300 pg/mL) was determined at four temperatures, namely 5 °C, room temperature (25 °C), 40 °C and 50 °C.
  • the stability of the samples was determined by investigating the appearance, odour, pH measured at 25 °C and the density indicating either water loss (WL) or solid gain (SG) measured at 25 °C.
  • the viscosity of the formulation was determined at 25 °C.
  • the stability was determined over a period of 12 weeks and inspected at 1 , 2, 4, 6, 8 and 12 weeks.
  • the formulation was prepared as follows: 10 g of CarbopolTM Ultrez 21 was dissolved in 4165 mL of dH20 and mixed at a slow speed using a homogeniser. While the mixture was being stirred 100 g glycerine was added. MyritolTM 318 (250 g), isopropyl myristate (25 g), CetiolTM CC (75 g) and NovemerTM EC-1 polymer (50 g) were mixed in a separate container and then added to the main mixture, while mixing with moderate agitation. EuxylTM PE 9010 was slowly added to the mixture until a uniform gel-cream was obtained.
  • the appearance and odour of the samples were determined through sensory analysis.
  • the variation in pH was determined using a pH meter suited for formulations.
  • the pH meter was first calibrated at pH 2, pH 4 and pH 7, and thereafter the pH of the extract and the formulation was determined.
  • the electrode was rinsed between samples with standard rinse aid.
  • the density was measured using a Mettler PM4800 DeltaRange® scale and a Sheen 1501/100 Pyknometer (S283830). The Pyknometer measured precisely 100 mL of the sample and water.
  • the density (p S am P ie) of the sample was determined with the following calculation, where p wa ter indicates the density of water: ( Mass of pyknometer filled with sample ) — (mass of clean, dry pyknometer )
  • the viscosity of the formulation was determined using a rotational viscometer at 10 rpm (Rotation Per Minute) and measured in centipoise (cP).
  • the ethanolic extract of A. linearis started to darken at week 6 when stored at 25 °C, 40 °C and 50 °C, while the formulation darkened at week 4 when stored at 25 °C and at week 1 when stored at 40 °C and 50 °C.
  • the colour change is possibly due to the oxidation and degradation of the phenolic compounds present in the extract. Phenolic compounds have been reported for their vast odour complexes in food, which changes depending on the different exposure to high temperatures.
  • the initial odour of the ethanolic extract of A. linearis alone and in the formulation was similar to a herbal tea odour. This odour remained constant over the 12 weeks at the different concentrations tested for the formulation but became slightly stronger in the extract after 12 weeks at 40 °C and after 6 weeks at 50 °C (Table 3 and 4).
  • Table 3 The stability of the ethanolic extract of Aspalathus linearis (Burm.f.) R.Dahlgren determined over 12 weeks in glass jars.
  • Table 4 The stability of the ethanolic extract of Aspalathus linearis (Burm.f.) R.Dahlgren, 5% in a cream gel formulation determined over 12 weeks in glass jars.
  • the ethanolic extract of A. linearis in a finished formulation was submitted to Dermscan Eurofins, a French company, for clinical studies.
  • the clinical studies were conducted at Insight Research Laboratories in Mauritius.
  • the clinical study was conducted on 30 individuals (ages ranged from 20 to 60 years) having a skin phototype of I to VI, with the majority having V or VI Fitzpatrick skin types.
  • the study included subjects with localized depigmented areas on face, limbs and other parts of the body.
  • the individuals (both male and female) were divided into three groups, the first group received the placebo, the second group received the ethanolic extract of A. linearis at a concentration of 100 pg/mL in the finished formulation and the third group received the ethanolic extract of A. linearis at a concentration of 200 pg/mL in the finished formulation.
  • the samples were prepared as described in Example 6 above. Briefly, 10 g of Carbopol Ultrez 21 was dissolved in 4165 mL of dFI20 and mixed at a slow speed using a homogeniser. While the mixture was being stirred, 100 g glycerine was added.
  • Myritol 318 250 g
  • isopropyl myristate 25 g
  • Cetiol CC 75 g
  • Novemer EC-1 polymer 50 g
  • Euxyl PE 9010 was slowly added to the mixture until a uniform gel-cream was obtained. Thereafter, the ethanolic extract of A. linearis was added to the gel cream as set out in Table 5.
  • the pigmentation of the skin was measured using Mexametre MX18® at the start of the clinical study and at day 56 (end of the study).
  • Table 5 Preparation of the samples submitted to Dermscan for clinical studies on hypopigmented patients.
  • Tested product 2 (AL 200), which resulted in an increase of 10% in the mean melanin index after 56 days of product use. It was reported that 67% of the patients presented an improvement in skin repigmentation. The results for the two concentrations indicated that the efficacy was not linked to a dose response. A nonsignificant increase of 3% in the mean melanin index was observed for the placebo after 56 days of product use.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Epidemiology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Medicinal Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Natural Medicines & Medicinal Plants (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Dermatology (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • Birds (AREA)
  • Microbiology (AREA)
  • Biotechnology (AREA)
  • Botany (AREA)
  • Mycology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Medical Informatics (AREA)
  • Alternative & Traditional Medicine (AREA)
  • Organic Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Biochemistry (AREA)
  • Molecular Biology (AREA)
  • Dispersion Chemistry (AREA)
  • Inorganic Chemistry (AREA)
  • Emergency Medicine (AREA)
  • Medicines Containing Plant Substances (AREA)

Abstract

La présente invention se rapporte à une composition topique comprenant un extrait éthanolique à 100 µg/ml de la plante Aspalathus linearis conjointement avec un vecteur dermatologiquement acceptable destinée à être utilisée dans une méthode de prévention ou de traitement d'un trouble hypopigmentaire de la peau chez un sujet, consistant à appliquer la composition topique sur la peau du sujet. L'invention se rapporte en outre à des méthodes de prévention ou de traitement d'un trouble hypopigmentaire de la peau chez un sujet, consistant à appliquer la composition topique sur la peau du sujet.
PCT/IB2022/055989 2021-06-28 2022-06-28 Compositions destinées au traitement de l'hypopigmentation WO2023275740A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
US18/574,200 US20240285710A1 (en) 2021-06-28 2022-06-28 Compositions for the treatment of hypopigmentation

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GB2109297.8A GB2608372A (en) 2021-06-28 2021-06-28 Compositions for the treatment of hypopigmentation
GB2109297.8 2021-06-28

Publications (1)

Publication Number Publication Date
WO2023275740A1 true WO2023275740A1 (fr) 2023-01-05

Family

ID=77179702

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/IB2022/055989 WO2023275740A1 (fr) 2021-06-28 2022-06-28 Compositions destinées au traitement de l'hypopigmentation

Country Status (3)

Country Link
US (1) US20240285710A1 (fr)
GB (1) GB2608372A (fr)
WO (1) WO2023275740A1 (fr)

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20080247974A1 (en) * 2005-01-31 2008-10-09 Raps Gmbh & Co. Kg Rooibos Extract with Increased Aspalathin Content, Process for the Preparation of Such a Rooibos Extract , and Cosmetic Agent Containing Such a Rooibos Extract
US20170056309A1 (en) * 2015-08-25 2017-03-02 Jan Marini Skin Research Luminate face mask
GB2562302A (en) * 2017-05-12 2018-11-14 Univ Pretoria Aspalathus linearis extracts for melanin stimulation

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH06128121A (ja) * 1992-10-15 1994-05-10 Sansho Seiyaku Co Ltd 化粧料

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20080247974A1 (en) * 2005-01-31 2008-10-09 Raps Gmbh & Co. Kg Rooibos Extract with Increased Aspalathin Content, Process for the Preparation of Such a Rooibos Extract , and Cosmetic Agent Containing Such a Rooibos Extract
US20170056309A1 (en) * 2015-08-25 2017-03-02 Jan Marini Skin Research Luminate face mask
GB2562302A (en) * 2017-05-12 2018-11-14 Univ Pretoria Aspalathus linearis extracts for melanin stimulation

Non-Patent Citations (6)

* Cited by examiner, † Cited by third party
Title
BLOM A ET AL: "Medicinal plants for Progressive Macular Hypomelanosis", SOUTH AFRICAN JOURNAL OF BOTANY - SUID-AFRIKAANS TYDSKRIFT VIRPLANTKUNDE, vol. 98, 1 May 2015 (2015-05-01), SA, pages 172 - 172, XP055951491, ISSN: 0254-6299, DOI: 10.1016/j.sajb.2015.03.019 *
CARDINALI G.BOLASCO G.ASPITE N.LUCANIA G.LOTTI L.V.TORRISI M.R.PICARDO M.: "Melanosome transfer promoted by keratinocyte growth factor in light and dark skin-derived keratinocytes", JOURNAL OF INVESTIGATIVE DERMATOLOGY, vol. 128, no. 3, 2008, pages 558 - 567
MATSUDA, H.KAWAGUCHI, Y.YAMAZAKI, M.HIRATA, N.NARUTO, S.ASANUMA, Y.KAIHATSU, T.KUBO, M.: "Melanogenesis stimulation in murine B16 melanoma cells by Piper nigrum leaf extract and its lignan constituents", BIOLOGICAL AND PHARMACEUTICAL BULLETIN, vol. 27, 2004, pages 1611 - 1616
MORTELMANS, K.ZEIGER, E.: "The Ames Salmonella/microsome mutagenicity assay", MUTAT. RES., vol. 455, 2000, pages 29 - 60, XP001152523, DOI: 10.1016/S0027-5107(00)00064-6
PURVES, D.HARVEY, C.TWEATS, D.LUMLEY, C.E.: "Genotoxicity testing: current practices and strategies used by the pharmaceutical industry", MUTAGENESIS, vol. 10, 1995, pages 297 - 312
VAN DER MERWE, J.JOUBERT, E.RICHARDS, E.MANLEY, M.SNIJMAN, P.MARNEWICK, J.L.GELDERBLOM, W.: "A comparative study on the antimutagenic properties of aqueous extracts of Aspalathus linearis (Rooibos), different Cyclopia spp.(honeybush) and Camellia sinensis teas", MUTAT. RES., vol. 611, 2006, pages 42 - 53, XP028035055, DOI: 10.1016/j.mrgentox.2006.06.030

Also Published As

Publication number Publication date
GB2608372A (en) 2023-01-04
GB202109297D0 (en) 2021-08-11
US20240285710A1 (en) 2024-08-29

Similar Documents

Publication Publication Date Title
EP2316413B1 (fr) Compositions comprenant un inhibiteur de NFkB et un promoteur du collagène non rétinoïde
EP1457780A1 (fr) Medicaments permettant d'ameliorer le prurit, la rugosite de l'epiderme ou l'hypersensibilite epidermique ou de blanchir par inhibition de la production et de la liberation du facteur de cellules souches
US20160095815A1 (en) Substance for restoring normal co-expression and interaction between the lox and nrage proteins
US6184199B1 (en) Active synergetic complex and cosmetic and/or pharmaceutical product containing this complex
JPH04342519A (ja) 美白剤
EP3574893A1 (fr) Compositions cosmétiques comprenant des plantes marines
KR101860109B1 (ko) 플로랄진세노사이드를 함유하는 피부 외용제 조성물
KR101026879B1 (ko) 피부주름개선용 화장료 조성물의 제조방법
WO2017217695A1 (fr) Composition comprenant l'alpha-garcinia mangostana, le bêta-garcinia mangostana, le gamma-garcinia mangostana, ou le composé gartanin utilisé comme ingrédient efficace pour atténuer les rides de la peau ou pour hydrater la peau
KR101558182B1 (ko) 흰감국 추출물을 함유하는 피부 외용제 조성물
KR101187559B1 (ko) 혼합 생약 발효 추출물을 함유하는 화장료 조성물
AU2021252728A1 (en) Composition for suppressing cellular senescence, and method for suppressing cellular senescence
US20240285710A1 (en) Compositions for the treatment of hypopigmentation
CN112190515A (zh) 黑米萃取发酵物及其制备与应用
CN116459172A (zh) 蔓荆子黄素的抗糖化应用
KR20090097550A (ko) 슈잔드린 및 이 추출물을 유효성분으로 함유하는 화장료조성물
KR20140145709A (ko) 항노화 및 주름개선에 활성을 갖는 대추붉은덕다리버섯 발효액 및 이를 유효성분으로 함유하는 의약품 및 향장 원료
US9668961B2 (en) Screening method and substances for contrasting aging
KR102034436B1 (ko) 베트남 후피향 추출물을 포함하는 아토피 피부염 치료 및 예방용 조성물
GB2562302A (en) Aspalathus linearis extracts for melanin stimulation
CN113226264A (zh) 用于减少内皮素-1分泌、干细胞因子合成和蛋白质羰基化的白松树皮提取物
KR20160000318A (ko) 전나무 오일을 포함하는 화장료 조성물
KR101877803B1 (ko) 플로랄진세노사이드를 함유하는 피부 외용제 조성물
KR101996962B1 (ko) 멜라닌 형성 억제제를 함유하는 피부 외용제 조성물
WO2017145958A1 (fr) Agent de blanchiment comprenant du syzygium polyanthum ou un extrait de celui-ci utilisé comme principe actif

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 22743570

Country of ref document: EP

Kind code of ref document: A1

WWE Wipo information: entry into national phase

Ref document number: 18574200

Country of ref document: US

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 22743570

Country of ref document: EP

Kind code of ref document: A1